36 results about "Velpatasvir" patented technology

The invention provides two synthetic methods for a Velpatasvir key intermediate 3 and further provides a new compound I and a new compound I3 for preparing the intermediate 3. Please see the structures of the three compounds in description.

The invention discloses a Velpatasvir intermediate, a preparation method thereof and a preparation of Velpatasvir. The invention provides a preparation method of a Velpatasvir intermediate compound 6,which comprises the the step: performing a reaction of nucleophilic substitution on a compound 8 and a compound 7 in an organic solvent under a condition that alkali exists under the protection of protective gas, so as to obtain the compound 6. The preparation method provided by the invention is mild in reaction conditions and simple and safe in operation and does not need special purification equipment, column chromatography isolation operation in an aftertreatment process is avoided, and a chiral isomer is controlled easily; and the yield is high, the chemical and optical purity of Velpatasvir 1 prepared from the intermediate compound 6 are greater than 99.50%, and all impurities are less than 0.10%, so that the Velpatasvir 1 can reach the crude drug standard, is low in cost and is suitable for industrial production.

The invention provides a method for re-crystallizing a key intermediate of a hepatitis C virus drug velpatasvir. Highly pure 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[D]naphtho[2,3-B]pyran-8(9H)-one is obtained, and parts of organic solvents can be recovered, so the method is economical and environmentally friendly. The method concretely includes the following steps: dissolving crude 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[D]naphtho[2,3-B]pyran-8(9H)-one in a mixed solvent containing a high-solubility organic solvent A and a low-solubility organic solvent B under a 35-70 DEG Cheating condition, precipitating crystals by a gradient cooling technology, centrifuging the obtained system, carrying out vacuum drying on the obtained wet solid at 30-70 DEG C, and performing normalpressure distillation on the obtained centrifugal mother liquor to recover the solvent B.

The invention relates to the technical field of medicine, in particular to a synthesis method of a velpatasvir intermediate A. Proper reactants are selected for synthesis of the velpatasvir intermediate A, a linear synthesis mode is changed into a convergence synthesis mode, and the method is mild in reaction condition, simple in step, high in synthesis efficiency, environmentally friendly and beneficial to industrial production and has good application prospects and market potentials. Besides, the invention also provides an intermediate compound for synthesizing the velpatasvir intermediate A.

The invention provides two synthetic methods for a Velpatasvir key intermediate 3 and further provides a new compound I and a new compound I3 for preparing the intermediate 3. Please see the structures of the three compounds in description.

The invention relates to a method for detecting velpatasvir related substances. Gradient elution can be carried out by taking a phosphoric acid aqueous solution and acetonitrile as mobile phases, andvelpatasvir can be effectively separated from the related substances.

The invention discloses a preparation method of an anti-hepatitis C medicine Velpatasvir intermediate 10,11-dihydro-5H-benzo[d]naphtha[2,3-b]pyranone derivative which is 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one (V). The preparation method concretely comprises the following steps: carrying out coupling cyclization on a raw material 7-((2-bromo-5-chlorophenyl)oxo)-3,4-dihydronaphthalen-1(2H)-one under the action of a ligand and an alkali to synthesize 3-chloro-10,11-dihydro-5H-benzo[d]naphtho[2,3-b]pyran-8(9H)-one, substituting chlorine by using sodium cyanide to form cyanide, prearing an organic acid from the cyanide under the action of an alkali, processing the organic acid by a lithium methide reagent to obtain 3-acetyl-10,11-dihydro-5H-benzo[d]naphtho[2,3-b] ]pyran-8(9H)-one, and carrying out a two-step bromination reaction to obtain the anti-hepatitis C medicine Velpatasvir intermediate. The method provides a brand new synthesis route of the anti-hepatitis C medicine Velpatasvir intermediate, and has the advantages of easily controlled reaction steps, and realization of stable industrial production preparation.

Disclosed is a preparation method for a compound shown by formula (E), a Velpatasvir intermediate shown by formula (K) and an analogue thereof. The method of the present invention uses inexpensive and easily available materials, and a simple process operation, without the need for separating the intermediates, the products are by column chromatography, and it is suitable for industrialized large-scale production..

The present invention relates to a preparation method of velpatasvir and its derivatives, specifically, the present invention prepares velpatasvir and its derivatives through the intermediate compound shown in the following formula (the definition of each group is as in the specification mentioned). The method has few by-products and low cost, and is suitable for industrial production of velpatasvir.

The invention provides a novel synthesis method of hepatitis drug velpatasvir.Two intermediate compounds including a compound 4 and a compound III are utilized to synthesize the velpatasvir, the structures of the two compounds are as shown in the following formulas, wherein PG radical is t-butyloxycarboryl (Boc), carboxybenzyl (Cbz), acetyl, benzoyl or (S)-2-methoxyl acyl carbonyl amino-3-methyl-butyryl group (Moc-L-Valyl).

The invention provides a method for re-crystallizing a key intermediate of a hepatitis C virus drug velpatasvir. Highly pure 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[D]naphtho[2,3-B]pyran-8(9H)-one is obtained, and parts of organic solvents can be recovered, so the method is economical and environmentally friendly. The method concretely includes the following steps: dissolving crude 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-benzo[D]naphtho[2,3-B]pyran-8(9H)-one in a mixed solvent containing a high-solubility organic solvent A and a low-solubility organic solvent B under a 35-70 DEG Cheating condition, precipitating crystals by a gradient cooling technology, centrifuging the obtained system, carrying out vacuum drying on the obtained wet solid at 30-70 DEG C, and performing normalpressure distillation on the obtained centrifugal mother liquor to recover the solvent B.

The invention discloses a preparation method of a benzochromene derivative shown as a formula (I). The benzochromene derivative can be taken as a synthesis intermediate of a drug such as a synthesis intermediate of Velpatasvir. Cheap and available 2-fluoro halogenated benzene is taken as a starting material, a brand-new synthetic route for preparing the benzochromene derivative is provided, the total yield of the whole reaction route is high, and the method is suitable for large-scale industrial production.